Fig. 3.
TRAIL is associated with Aβ1−42 in vivo, and mediates Aβ-induced neurotoxicity. (A) Images of Aβ1−42 at 3 and 6 months in male and female subiculum. N = 7 male and 7 female at 3 mo. N = 8 male and 5 female at 6 mo. (B) Aβ1−42 was increased in the subiculum with age in both sexes. Age effect: F1,23=44.6, p < 0.0001 (C) Images of TRAIL at 3 and 6 months in 5xFAD male and female subiculum. (D) Female 5xFAD mice showed an increase in TRAIL from 3 to 6 months. Sex effect: F1,24=9.2, p < 0.01, **p < 0.01 Sidak’s post-test. Scale bar 100 μm. (E) A positive correlation was seen between TRAIL and Aβ1−42 across all subjects. R = 0.42, *p < 0.05. (F) TRAIL and Aβ1−42 showed a strong positive correlation at 3 months in dentate gyrus. R = 0.6, *p < 0.05. (G) Images of HEBSCs treated with Aβ1−42 +/- αTRAIL. (H) Aβ1−42 caused robust neuronal injury that was blocked by αTRAIL but not isotype control antibodies. F3,59=13.1, p < 0.0001. N = 10–22 slices/group, 2 experiments combined. (I) Aβ1−42 increases in media glutamate were blocked by αTRAIL antibodies. F2,13=21.2, N = 3–7 wells/group p < 0.0001. **, p < 0.01, ****p < 0.0001, Sidak’s post-test